The anthropometric definition of the rectum is highly variable.

PURPOSE: The precise definition of the rectum is essential for localizing colorectal pathology, yet current definitions are nebulous. The objective of this study is to determine the anthropometric definition of common pelvic landmarks in relation to patient characteristics. METHODS: Seventy-one patients underwent open proctectomy with intra-operative measurements from the anal verge to various pelvic landmarks, and patient characteristics were evaluated. Analyses were performed using Spearman correlation and Wilcoxon rank sum. RESULTS: The mean landmark distance was dentate line = 1.7 cm (range 0.8-4.0 cm), puborectalis muscle = 4.2 cm (range 2.0-8.0 cm), anterior peritoneal reflection = 13.2 cm (range 8.5-21.0 cm), sacral promontory = 17.9 cm (range 13.0-26.0 cm), and confluence of the taenia = 25.5 cm (range 16.0-44.0 cm). Men had longer mean distances to the dentate line (p = 0.0003), puborectalis muscle (p = 0.03), and anterior peritoneal reflection (p = 0.02). Patient weight significantly correlated with distance to all landmarks except for the confluence of the taenia, which did not correlate with any patient factor. CONCLUSIONS: The location of common pelvic landmarks is highly variable. The use of predefined absolute measurements from the anal verge to localize rectal pathology is inaccurate and fails to account for patient variability.

Expression of RORγt marks a pathogenic regulatory T cell subset in human colon cancer.

The role of regulatory T cells (T(regs)) in human colon cancer (CC) remains controversial: high densities of tumor-infiltrating T(regs) can correlate with better or worse clinical outcomes depending on the study. In mouse models of cancer, T(regs) have been reported to suppress inflammation and protect the host, suppress T cells and protect the tumor, or even have direct cancer-promoting attributes. These different effects may result from the presence of different T(reg) subsets. We report the preferential expansion of a T(reg) subset in human CC with potent T cell-suppressive, but compromised anti-inflammatory, properties; these cells are distinguished from T(regs) present in healthy donors by their coexpression of Foxp3 and RORγt. T(regs) with similar attributes were found to be expanded in mouse models of hereditary polyposis. Indeed, ablation of the RORγt gene in Foxp3(+) cells in polyp-prone mice stabilized T(reg) anti-inflammatory functions, suppressed inflammation, improved polyp-specific immune surveillance, and severely attenuated polyposis. Ablation of interleukin-6 (IL-6), IL-23, IL-17, or tumor necrosis factor-α in polyp-prone mice reduced polyp number but not to the same extent as loss of RORγt. Surprisingly, loss of IL-17A had a dual effect: IL-17A-deficient mice had fewer polyps but continued to have RORγt(+) T(regs) and developed invasive cancer. Thus, we conclude that RORγt has a central role in determining the balance between protective and pathogenic T(regs) in CC and that T(reg) subtype regulates inflammation, potency of immune surveillance, and severity of disease outcome.

Incorporating fertility preservation into the care of young oncology patients.

As the number of cancer survivors continues to increase, oncologists are faced with the challenge of providing cancer therapy to patients who may 1 day want to have children. Yet, gonadotoxic cancer treatments can compromise future fertility, either temporarily or permanently. There are established means of preserving fertility before cancer treatment; specifically, sperm cryopreservation for men and in vitro fertilization and embryo cryopreservation for women. Several innovative techniques are being actively investigated, including oocyte and ovarian follicle cryopreservation, ovarian tissue transplantation, and in vitro follicle maturation, which may expand the number of fertility preservation choices for young cancer patients. Fertility preservation may also require some modification of cancer therapy; thus, patients' wishes regarding future fertility and available fertility preservation alternatives should be discussed before initiation of therapy. This commentary provides an overview of the range of fertility preservation options currently available and under development, using case-based discussions to illustrate ways in which fertility preservation can be incorporated into oncology care. Cases involving breast cancer, testicular cancer, and rectal cancer are described to illustrate fertility issues experienced by male and female patients, as well as to provide examples of strategies for modifying surgical, medical, and radiation therapy to spare fertility. Current guidelines in oncology and reproductive medicine are also reviewed to underscore the importance of communicating fertility preservation options to young patients with cancer.

HIV and anal cancer outcomes: a single institution's experience.

PURPOSE: The purpose of this study is to identify the effect of HIV status on outcome of treatment for squamous-cell carcinoma of the anal canal. METHODS: A retrospective review was performed on all patients with squamous-cell carcinoma of the anal canal treated at a single academic institution between January 1996 and December 2006. RESULTS: Our search identified 87 (21 HIV-positive) patients who had invasive squamous-cell cancer. The median follow-up was 38 months. Eighty-five percent of HIV-negative patients and 81 percent of HIV-positive were identified as complete responders at 6 weeks after completion of combined modality therapy. Eight percent of HIV-negative and 29 percent of HIV-positive patients developed recurrent disease after 6 months (P = 0.0009). Overall survival for HIV-negative and HIV-positive patients was 71 percent and 73 percent, respectively. CONCLUSIONS: HIV-positive patients respond equally to combined modality therapy but have recurrences more frequently than patients who are HIV negative. Overall survival in these two groups is equivalent.

Use and outcomes of laparoscopic-assisted colectomy for cancer in the United States.

BACKGROUND: Laparoscopic-assisted colectomy (LAC) has gained acceptance for the treatment of colon cancer. However, long-term outcomes of LAC have not been examined at the national level outside of experienced centers. OBJECTIVE: To compare use and outcomes of LAC and open colectomy (OC). DESIGN: Retrospective cohort study. SETTING: National Cancer Data Base. PATIENTS: Patients who underwent LAC (n = 11 038) and OC (n = 231 381) for nonmetastatic colon cancer (1998-2002). MAIN OUTCOME MEASURES: Regression methods were used to assess use and outcomes of LAC compared with OC. RESULTS: Laparoscopic-assisted colectomy use increased from 3.8% in 1998 to 5.2% in 2002 (P < .001). Patients were significantly more likely to undergo LAC if they were younger than 75 years, had private insurance, lived in higher-income areas, had stage I cancer, had descending and/or sigmoid cancers, or were treated at National Cancer Institute-designated hospitals. Compared with those undergoing OC, patents undergoing LAC had 12 or more nodes examined less frequently (P < .001), similar perioperative mortality and recurrence rates, and higher 5-year survival rates (64.1% vs 58.5%, P < .001). After adjusting for patient, tumor, treatment, and hospital factors, 5-year survival was significantly better after LAC compared with OC for stage I and II but not for stage III cancer. Highest-volume centers had comparable short- and long-term LAC outcomes compared with lowest-volume hospitals, except highest-volume centers had significantly higher lymph node counts (median, 12 vs 8 nodes; P < .001). CONCLUSIONS: Laparoscopic-assisted colectomy and OC outcomes are generally comparable in the population. However, survival was better after an LAC than after an OC in select patients.

Laparoscopic colectomy for cancer is not inferior to open surgery based on 5-year data from the COST Study Group trial.

PURPOSE: Oncologic concerns from high wound recurrence rates prompted a multi-institutional randomized trial to test the hypothesis that disease-free and overall survival are equivalent, regardless of whether patients receive laparoscopic-assisted or open colectomy. METHODS: Eight hundred seventy-two patients with curable colon cancer were randomly assigned to undergo laparoscopic-assisted or open colectomy at 1 of 48 institutions by 1 of 66 credentialed surgeons. Patients were followed for 8 years, with 5-year data on 90% of patients. The primary end point was time to recurrence, tested using a noninferiority trial design. Secondary endpoints included overall survival and disease-free survival. (Kaplan-Meier) RESULTS: As of March 1, 2007, 170 patients have recurred and 252 have died. Patients have been followed a median of 7 years (range 5-10 years). Disease-free 5-year survival (Open 68.4%, Laparoscopic 69.2%, P=0.94) and overall 5-year survival (Open 74.6%, Laparoscopic 76.4%, P=0.93) are similar for the 2 groups. Overall recurrence rates were similar for the 2 groups (Open 21.8%, Laparoscopic 19.4%, P=0.25). These recurrences were distributed similarly between the 2 treatment groups. Sites of first recurrence were distributed similarly between the treatment arms (Open: wound 0.5%, liver 5.8%, lung 4.6%, other 8.4%; Laparoscopic: wound 0.9%, liver 5.5%, lung 4.6%, other 6.1%). CONCLUSION: Laparoscopic colectomy for curable colon cancer is not inferior to open surgery based on long-term oncologic endpoints from a prospective randomized trial.

Preoperative chemoradiation for rectal cancer: results of multimodality management and analysis of prognostic factors.

BACKGROUND: Our goals were to examine the impact of neoadjuvant chemoradiation for rectal cancer on surgical outcomes and to determine prognostic factors predicting improved survival. METHODS: Retrospective cohort of 56 male and 44 female patients. RESULTS: After preoperative chemoradiation, 73% of patients had sphincter-preserving surgery. The 5-year disease-free (DFS) and overall survival rates were 77% and 81%, respectively. Twenty-five percent of patients showed a complete pathologic response. T-level downstaging and pathologic T stage did not correlate with recurrence or survival rates. Pathologic nodal stage was associated with a significant difference in recurrence rates (N(0) 19%, N1 20%, and N2 75%, P = .038) and DFS (N0/N1 vs. N2, 79% vs. 25%, P = .002). CONCLUSION: Neoadjuvant chemoradiation resulted in a high rate of sphincter preservation. Complete pathologic responses after surgery were frequent and although pathologic T stage after surgery did not affect recurrence rates, pathologic nodal response was associated with improved recurrence and survival rates.

A comparison of laparoscopically assisted and open colectomy for colon cancer.

BACKGROUND: Minimally invasive, laparoscopically assisted surgery was first considered in 1990 for patients undergoing colectomy for cancer. Concern that this approach would compromise survival by failing to achieve a proper oncologic resection or adequate staging or by altering patterns of recurrence (based on frequent reports of tumor recurrences within surgical wounds) prompted a controlled trial evaluation. METHODS: We conducted a noninferiority trial at 48 institutions and randomly assigned 872 patients with adenocarcinoma of the colon to undergo open or laparoscopically assisted colectomy performed by credentialed surgeons. The median follow-up was 4.4 years. The primary end point was the time to tumor recurrence. RESULTS: At three years, the rates of recurrence were similar in the two groups--16 percent among patients in the group that underwent laparoscopically assisted surgery and 18 percent among patients in the open-colectomy group (two-sided P=0.32; hazard ratio for recurrence, 0.86; 95 percent confidence interval, 0.63 to 1.17). Recurrence rates in surgical wounds were less than 1 percent in both groups (P=0.50). The overall survival rate at three years was also very similar in the two groups (86 percent in the laparoscopic-surgery group and 85 percent in the open-colectomy group; P=0.51; hazard ratio for death in the laparoscopic-surgery group, 0.91; 95 percent confidence interval, 0.68 to 1.21), with no significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer. Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group, as reflected by a shorter median hospital stay (five days vs. six days, P<0.001) and briefer use of parenteral narcotics (three days vs. four days, P<0.001) and oral analgesics (one day vs. two days, P=0.02). The rates of intraoperative complications, 30-day postoperative mortality, complications at discharge and 60 days, hospital readmission, and reoperation were very similar between groups. CONCLUSIONS: In this multi-institutional study, the rates of recurrent cancer were similar after laparoscopically assisted colectomy and open colectomy, suggesting that the laparoscopic approach is an acceptable alternative to open surgery for colon cancer.

Comparative analysis of cell adhesion molecules, cell cycle regulatory proteins, mismatch repair genes, cyclooxygenase-2, and DPC4 in carcinomas arising in inflammatory bowel disease and sporadic colon cancer.

Colon carcinoma arising in inflammatory bowel disease often exhibits aggressive behavior compared to sporadic carcinomas. The rationale for the different biological behaviors of these two groups of tumors is not fully understood. In this study, we have examined carcinomas arising in inflammatory bowel disease (IBD) and sporadic carcinomas (SCA) for molecular differences that may provide clues for the behavioral disparity of these tumors. Thirty-eight colon carcinomas (12 from ulcerative colitis, 5 from Crohn's disease, and 21 SCA) were analyzed by immunohistochemistry for cell adhesion molecules (E-cadherin, beta-catenin, CD44), cell cycle regulatory proteins (cyclin D1, p27, p21), mismatch repair proteins (hMLH1, hMSH2), cyclooxygenase-2 and DPC4. Carcinomas arising in IBD showed significant decrease in expression of cell adhesion molecules, the cell cycle inhibitor protein, p21, and increased expression of cyclooxygenase-2 compared to sporadic carcinomas. No differences were observed in the expression of cell cycle regulatory proteins p27, cyclin D1, DPC4 and mismatch repair proteins between these two groups of tumors. Decreased expression of p21 as well as adhesion molecules may provide increased impetus for the aggressive behavior of tumors arising in inflammatory bowel disease.

Accuracy of endoscopic ultrasound for restaging rectal cancer following neoadjuvant chemoradiation therapy.

OBJECTIVES: Endoscopic ultrasound (EUS) provides important information in the initial staging of patients with rectal cancer. Preoperative combined modality chemotherapy and radiation (neoadjuvant therapy) for patients with locally advanced rectal cancer may reduce local recurrence and improve survival. The accuracy of EUS restaging of rectal cancer after chemoradiation has not been extensively studied and its usefulness is unclear. The aim of this study was to verify the accuracy of EUS in staging rectal cancer after neoadjuvant chemoradiation in a large cohort of patients. METHODS: EUS staging was performed before and after concurrent 5-fluorouracil and hyperfractionated radiotherapy in 82 patients with recently diagnosed locally advanced rectal cancer. All patients underwent subsequent surgical resection and complete pathologic staging. RESULTS: After chemoradiation, 16 patients (20%) had no residual disease at pathologic staging. (T0N0). However, EUS correctly predicted complete response to chemoradiation in only 10 of 16 patients (63%). Overall accuracy of EUS post chemoradiation for pathologic T-stage was only 48%. Fourteen percent were understaged and 38% overstaged. EUS accuracy for N-stage was 77%. The T-category was correctly staged before surgery in 23 of the 56 responders (41%) and in 16 of 24 nonresponders (67%). EUS was unable to accurately distinguish postradiation changes from residual tumor. CONCLUSION: EUS staging of rectal cancer after chemoradiation is inaccurate, especially in the group of patients with visual and EUS evidence of response. Its routine use for staging purposes after neoadjuvant chemoradiation for rectal cancer should be discouraged.